The effect of a single remote injection of statin-impregnated poly (lactic-co-glycolic acid) microspheres on osteogenesis around titanium implants in rat tibia

Biodegradable polymers for dental tissue engineering and regeneration

“…Other applications of PLGA relate to better osteointegration of titanium implants through PLGA microparticles loaded with growth factors [161,162] and the treatment of alveolar bone resorption with bisphosphonate PLGA microspheres [163]. In particular, injectable PLGA microspheres containing fluvastatin enhanced osteogenesis around titanium implants in the rat tibia [164] and PLGA microparticles loaded with insulin improved biomechanical retention of implants on type I diabetic rats [165].…”

Novel applications of statins for bone regeneration

“…This is of particular interest in both the orthopedic and craniofacial fields, as metallic implants are common modes of fixation and reconstruction. Masuzaki et al found that fluvastatin-loaded microparticles injected at a distant site enhanced the osteogenesis around titanium rods implanted into a rat tibia [103]. This delivery technique was unique in that it utilized a local delivery vehicle to achieve systemic delivery through a non-parenteral and non-intravenous route.…”

“…While the models used are not precisely comparable, the discrepancy in results may be attributable in part to the disparity in total dosage provided to the animals. In the studies where positive effect of either fluvastatin or simvastatin was noted, whether locally delivered or orally delivered, the total dosage was determined by weight and supplied of the order of milligrams [103,105,108]. In the studies where negative or no effect was seen, simvastatin was supplied of the order of micrograms per implant, approximately a 1000-fold decrease compared to the studies that showed a positive effect [106,107].…”

“…Synthetic polymers are another alternative to naturally derived polymers and have the advantage of being highly modifiable and tunable, though they also lack natural environmental cues to direct tissue growth. Poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) are common synthetic polymer carriers for statins, either as microparticles or a membrane [103,124–126]. Stein et al combined hydrogel and poly(lactic acid) to locally deliver simvastatin to the lateral aspect of the rat mandible and investigated dose response, finding that a low dose applied locally could achieve bone growth while avoiding the inflammation that occurs with administration of high doses [19].…”

Release properties of atelocollagen-gelatin complexes as carriers for local administration of fluvastatin

“…However, simple direct administration of statins to the affected sites is not effective for osteoinduction because the drug diffuses into the surrounding tissues [5][6][7] . Accordingly, controlled release systems for statins are required for local administration of statins with carriers, such as gelatin, atelocollagen sponge (Teruplug ® ), α-TCP, β-TCP, HA, and PLGA [8][9][10][11] . In particular, gelatin is widely used as a drug carrier because of desirable characteristics including (1) proven safety, (2) wide application of this biodegradable material for clinical purposes, (3) different physical properties by chemical modification, and (4) ease of attaching to drugs [12][13][14][15] .…”